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Article

Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer’s Disease

by
Julia Doroszkiewicz
1,
Agnieszka Kulczyńska-Przybik
1,
Maciej Dulewicz
2,
Jan Mroczko
1,
Renata Borawska
1,
Agnieszka Słowik
3,
Henrik Zetterberg
2,4,5,6,7,8,
Jörg Hanrieder
2,5,9,
Kaj Blennow
2,4 and
Barbara Mroczko
1,10,*
1
Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland
2
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80 Mölndal, Sweden
3
Department of Neurology, Jagiellonian University, 30-688 Cracow, Poland
4
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 80 Mölndal, Sweden
5
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
6
UK Dementia Research Institute at UCL, London WC1N 3AR, UK
7
Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China
8
Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792-2460, USA
9
SciLifeLab, University of Gothenburg, 405 30 Gothenburg, Sweden
10
Department of Biochemical Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(14), 7543; https://doi.org/10.3390/ijms25147543
Submission received: 28 May 2024 / Revised: 3 July 2024 / Accepted: 5 July 2024 / Published: 9 July 2024
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: New Insights into Neuroproteins)
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Abstract

Recent investigations implicate neuroinflammatory changes, including astrocyte and microglia activation, as crucial in the progression of Alzheimer’s disease (AD) Thus, we compared selected proteins reflecting neuroinflammatory processes to establish their connection to AD pathologies. Our study, encompassing 80 subjects with (n = 42) AD, (n = 18) mild cognitive impairment (MCI) and (n = 20) non-demented controls compares the clinical potential of tested molecules. Using antibody-based methods, we assessed concentrations of NGAL, CXCL-11, sTREM1, and sTREM2 in cerebrospinal fluid (CSF). Proinflammatory proteins, NGAL, and CXCL-11 reached a peak in the early stage of the disease and allowed for the identification of patients with MCI. Furthermore, the concentration of the anti-inflammatory molecule sTREM2 was highest in the more advanced stage of the disease and permitted differentiation between AD and non-demented controls. Additionally, sTREM2 was biochemically linked to tau and pTau in the AD group. Notably, NGAL demonstrated superior diagnostic performance compared to classical AD biomarkers in discriminating MCI patients from controls. These findings suggest that proteins secreted mainly through microglia dysfunction might play not only a detrimental but also a protective role in the development of AD pathology.
Keywords: Alzheimer’s disease; microglia; astrocytes; NGAL; CXCL-11; sTREM1; sTREM2; neuroinflammation Alzheimer’s disease; microglia; astrocytes; NGAL; CXCL-11; sTREM1; sTREM2; neuroinflammation

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MDPI and ACS Style

Doroszkiewicz, J.; Kulczyńska-Przybik, A.; Dulewicz, M.; Mroczko, J.; Borawska, R.; Słowik, A.; Zetterberg, H.; Hanrieder, J.; Blennow, K.; Mroczko, B. Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer’s Disease. Int. J. Mol. Sci. 2024, 25, 7543. https://doi.org/10.3390/ijms25147543

AMA Style

Doroszkiewicz J, Kulczyńska-Przybik A, Dulewicz M, Mroczko J, Borawska R, Słowik A, Zetterberg H, Hanrieder J, Blennow K, Mroczko B. Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer’s Disease. International Journal of Molecular Sciences. 2024; 25(14):7543. https://doi.org/10.3390/ijms25147543

Chicago/Turabian Style

Doroszkiewicz, Julia, Agnieszka Kulczyńska-Przybik, Maciej Dulewicz, Jan Mroczko, Renata Borawska, Agnieszka Słowik, Henrik Zetterberg, Jörg Hanrieder, Kaj Blennow, and Barbara Mroczko. 2024. "Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer’s Disease" International Journal of Molecular Sciences 25, no. 14: 7543. https://doi.org/10.3390/ijms25147543

APA Style

Doroszkiewicz, J., Kulczyńska-Przybik, A., Dulewicz, M., Mroczko, J., Borawska, R., Słowik, A., Zetterberg, H., Hanrieder, J., Blennow, K., & Mroczko, B. (2024). Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer’s Disease. International Journal of Molecular Sciences, 25(14), 7543. https://doi.org/10.3390/ijms25147543

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